Robustness Evaluation of Deep Inspiration Breath-Hold (DIBH) Plans in Internal Mammary Irradiation

Official title

Robustness Evaluation of Deep Inspiration Breath-Hold (DIBH) Radiotherapy Plans for Internal Mammary Irradiation in Postoperative Breast Cancer

Overview

This study is an investigator-initiated, single-arm, single-center, prospective, observational study. The hypothesis is that during the implementation of deep inspiration breath-hold (DIBH) radiotherapy plans in postoperative breast cancer patients receiving internal mammary irradiation, the actual target dose coverage and organ-at-risk (OARs) dose parameters remain within clinically acceptable ranges.

Detailed description

For patients with left-sided breast cancer, postoperative radiotherapy can expose the heart to excessive radiation, increasing the risk of cardiac toxicity. DIBH displaces the heart away from the chest wall by expanding the thoracic cavity during breath-holding to reduce cardiac radiation doses. Although DIBH has demonstrated efficacy in reducing cardiac exposure in left-sided breast cancer, its application in internal mammary and regional lymph node irradiation remains uncertain due to potential issues related to dose robustness associated with larger target volumes near the heart.

The success of DIBH depends on maintaining a stable respiratory gating window; however, individual variations in breath-holding capacity and fatigue may lead to intrafractional and interfractional positional errors, which can compromise target coverage and increase doses to OARs. Surface-guided systems monitor respiratory motion but may not accurately represent the positions of deep-seated targets and OARs, raising concerns about dose coverage, particularly for the internal mammary target.

State-of-the art radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) provide improved dose conformality and reduce high-dose cardiac exposure. However, the integration of these techniques with DIBH and the impact of positional errors on dose robustness remain inadequately studied. Proton therapy, due to its steep dose fall-off, minimizes cardiac and pulmonary exposure but is highly sensitive to positional changes. This sensitivity may amplify uncertainties during DIBH, particularly in the context of internal mammary irradiation.

This study aims to evaluate the dose robustness of DIBH in left-sided breast cancer patients undergoing internal mammary irradiation, with a specific focus on the impact of respiratory motion amplitude during breath-holding on dose distribution, as well as intrafractional and interfractional positional errors. Using offline CT and Cone-Beam CT (CBCT) data, it will assess positional deviations and compare the performance of IMRT, VMAT, and Intensity-Modulated Proton Therapy (IMPT) during DIBH. The findings will provide critical evidence to optimize DIBH for internal mammary and regional lymph node irradiation, improving clinical outcomes while minimizing cardiac toxicity.

Interventions

• Radiation DIBH with 3mm Gating Window
  The patient will receive moderately hypofractionated radiotherapy targeting the ipsilateral breast, supraclavicular and internal mammary nodes, and high-risk axillary region, with a prescribed dose of 40 Gy (RBE) /15Fx. IMRT, VMAT, or proton therapy will be chosen based on the radiation oncologist's judgment and patient preference. Respiratory gating tolerance is set at ±1.5 mm (3 mm total). Three simulated CT scans during DIBH will assess gating window positions: CT1: Breath-hold at the cente
• Radiation DIBH with 2 mm Gating Window
  The patient will receive moderately hypofractionated radiotherapy targeting the ipsilateral breast, supraclavicular and internal mammary nodes, and high-risk axillary region, with a prescribed dose of 40 Gy (RBE) /15Fx. IMRT, VMAT, or proton therapy will be chosen based on the radiation oncologist's judgment and patient preference. Respiratory gating tolerance is set at ±1 mm (2 mm total). Three simulated CT scans during DIBH will assess gating window positions: CT1: Breath-hold at the center of
• Radiation DIBH with 1.5 mm Gating Window
  The patient will receive moderately hypofractionated radiotherapy targeting the ipsilateral breast, supraclavicular and internal mammary nodes, and high-risk axillary region, with a prescribed dose of 40 Gy (RBE) /15Fx. IMRT, VMAT, or proton therapy will be chosen based on the radiation oncologist's judgment and patient preference. Respiratory gating tolerance is set at ± 0.75 mm (1.5 mm total). Three simulated CT scans during DIBH will assess gating window positions: CT1: Breath-hold at the cen

Primary outcome measures

• Target coverage of the Planning treatment volume (PTV) [Time frame: Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.]

Secondary outcome measures (8)

• Additional dose-volume parameters of the PTV [Time frame: Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.]
• Dose-volume parameters of the organs at risk (OARs) [Time frame: Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.]
• Conformity Index (CI) of the PTV [Time frame: Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.]
• Homogeneity Index (HI) of the PTV [Time frame: Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.]
• Intra-fractional Error-PTV [Time frame: During each treatment fraction (daily, approximately 3-4 weeks per patient)]
• Intra-fractional Error-OARs [Time frame: During each treatment fraction (daily, approximately 3-4 weeks per patient)]
• Inter-fractional Error- PTV [Time frame: Across all treatment fractions (approximately 3-4 weeks per patient)]
• Inter-fractional Error- OAR [Time frame: Across all treatment fractions (approximately 3-4 weeks per patient)]

Eligibility criteria

Inclusion criteria

• Provide a signed and dated informed consent form (ICF) before the initiation of any trial-specific procedures.
• Female patients aged ≥ 18 years.
• Histologically confirmed invasive breast cancer.
• Have received breast-conserving surgery or mastectomy with axillary staging, including sentinel lymph node biopsy and/or axillary lymph node dissection.
• Able to hold breath for more than 30 seconds after deep inspiration.
• Planned to receive postoperative radiotherapy targeting regional lymph nodes, including the internal mammary nodes, under DIBH conditions.
• Planned to undergo moderate hypofractionated radiotherapy.
• Karnofsky Performance Status (KPS) score ≥ 80.
• The estimated life expectancy of greater than 5 years .
• Sufficient wound healing from surgery, with no signs of active infection at the intended radiation site.

Exclusion criteria

• Pregnant or breastfeeding women.
• Presence of any severe, uncontrolled comorbidity or medical condition that, in the investigator's judgment, would render the participant unsuitable for the study, compromise protocol compliance, or confound the interpretation of study results.
• Unable to understand or comply with breath-hold training instructions.
• Right-sided breast cancer.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai

Identifiers

NCT: NCT07498855 · RJBC-DIBH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗